This R21 proposal is in direct response to PA-12-157 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to encourage pilot and feasibility clinical and behavioral studies to evaluate interventions designed to improve the management of diabetes and it complications. People with diabetes mellitus (DM) are known to have a very high incidence of upper extremity joint and muscle impairments leading to pain and disability. Our preliminary survey data found that 63% (149 of 236) of people with DM attending an outpatient Diabetes Center reported shoulder pain or disability. Limited joint mobility (LJM) is a systemic complication of DM believed to be caused by thickening and stiffness of periarticular connective tissue. First observed in the hands of people with DM, LJM also may occur in the shoulder and be a precursor to severe shoulder pain and disability. Condensation of glucose and metabolic intermediates form non-enzymatic advanced glycation end-products (AGEs) and are thought to be the primary mechanism for this connective tissue thickening and LJM in people with DM. In addition to excessive AGE levels, a lack of active shoulder motion may be an important factor contributing to the etiology of shoulder LJM. The primary goal of this project is to determine how AGE accumulation and shoulder movement (humeral thoracic range of motion and activity count) interact to contribute to shoulder LJM, pain and disability, and if an intervention consisting of a tailored dose of stretching and active shoulder movement can reduce these problems in people with DM. A pilot randomized controlled trial will determine the effect size of a targeted upper extremity movement program on shoulder elevation, pain, and activity limitations in people with DM. This project will use an innovative and noninvasive imaging measure (skin intrinsic fluorescence) as a biomarker for AGE levels in the skin, three dimensional motion analysis to quantify limited motion of the glenohumeral joint, and accelerometers to quantify shoulder activity count throughout the day. The results will have important implications for understanding the metabolic and movement related causes of upper extremity joint and muscle impairments and also if purposeful movements can have an effect on these limitations in this patient group with substantial upper extremity pain and disability. The long term goal is to understand the common denominators of musculoskeletal problems in people with DM and investigate pharmacological and rehabilitative strategies to minimize resultant pain and disability.